title: PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer--results at the time of surgery.
abstract: BACKGROUND
  Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer. Strategies to improve efficacy include the use of anthracyclines, taxanes, and intensified dose with bone marrow support.
  
  
  METHODS
  Patients received neoadjuvant epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) followed by paclitaxel 175 mg/m(2) (EC→T), each 3-weekly for four cycles (n = 370), or epirubicin 150 mg/m(2) followed by paclitaxel 225 mg/m(2) with pegfilgrastim followed by CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), fluorouracil 600 mg/m(2)) on days 1 and 8 (E(dd)→T(dd)→CMF), each 2-weekly and for three cycles (n = 363). Patients were randomly allocated to either simultaneous darbepoetin alfa (DA) (n = 356) or none (n = 377).
  
  
  RESULTS
  Pathological complete response (pCR) rate (breast) was higher with E(dd)→T(dd)→CMF, 18.7% versus 13.2% with EC→T; P = 0.043, ypT0/Tis; ypN0 was reported in 20.9% versus 14.3% respectively; P = 0.019. Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate. Mean hemoglobin values maintained higher with DA (13.6 versus 12.6 g/dl). E(dd)→T(dd)→CMF regimen showed more grade 3-4 mucositis, sensory neuropathy, and neurological complaints. Thromboembolic events were more frequent on DA (3% versus 6%; P = 0.055).
  
  
  CONCLUSIONS
  Dose-dense and -intensified neoadjuvant chemotherapy with E(dd)→T(dd)→CMF was potentially superior to EC→T in terms of pCR. Primary use of DA did not affect pCR.
authors.affiliation: Department of Obstetrics and Gynecology, Helios Klinikum Berlin-Buch, Berlin. Electronic address: michael.untch@helios-kliniken.de.
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: P A
authors.initials: PA
authors.lastname: Fasching
authors.affiliation: Division of Hematology and Oncology, David Geffen School of Medicine at University of California, Los Angeles, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Konecny
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Großhadern, Munich.
authors.forename: F
authors.initials: F
authors.lastname: von Koch
authors.affiliation: Department of Obstetrics and Gynecology, St. Barbara Hospital, Hamm.
authors.forename: U
authors.initials: U
authors.lastname: Conrad
authors.affiliation: Hematologic/Oncologic Clinic, Wuppertal.
authors.forename: W
authors.initials: W
authors.lastname: Fett
authors.affiliation: University Women's Hospital of Ulm, Ulm.
authors.forename: C
authors.initials: C
authors.lastname: Kurzeder
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Hannover, Hannover.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lück
authors.affiliation: University Women's Hospital of Freiburg, Freiburg.
authors.forename: E
authors.initials: E
authors.lastname: Stickeler
authors.affiliation: City Hospital, Kassel.
authors.forename: H
authors.initials: H
authors.lastname: Urbaczyk
authors.affiliation: Department of Obstetrics and Gynecology, Protestant Hospital, Bergisch Gladbach.
authors.forename: B
authors.initials: B
authors.lastname: Liedtke
authors.affiliation: Hematologic/Oncologic Practice München.
authors.forename: C
authors.initials: C
authors.lastname: Salat
authors.affiliation: Department of Obstetrics and Gynecology, Technical University of Munich, Munich.
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Hamburg-Eppendorf, Hamburg.
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.affiliation: University Women's Hospital of Mainz, Mainz.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Großhadern, Munich.
authors.forename: S
authors.initials: S
authors.lastname: Hasmüller
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Großhadern, Munich.
authors.forename: M
authors.initials: M
authors.lastname: Lenhard
authors.affiliation: Institute for Medical Statistics and Epidemiology, Technical University Munich, Munich.
authors.forename: T
authors.initials: T
authors.lastname: Schuster
authors.affiliation: German Breast Group, Neu-Isenburg.
authors.forename: V
authors.initials: V
authors.lastname: Nekljudova
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lebeau
authors.affiliation: German Breast Group, Neu-Isenburg.
authors.forename: S
authors.initials: S
authors.lastname: Loibl
authors.affiliation: German Breast Group, Neu-Isenburg.
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D000069585:Filgrastim; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010349:Patient Compliance; D011092:Polyethylene Glycols; D011300:Preoperative Care; D011994:Recombinant Proteins / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D000068256:Darbepoetin alfa; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000069585:Filgrastim; D005472:Fluorouracil; D008727:Methotrexate